Signaling by nephrin requires the adaptor protein, Nck, and the actin nucleation-promoting factor, N-WASP, to stimulate actin polymerization necessary for efficient glomerular function. Disruptions to this signaling pathway result in nephrotic syndromes, which are characterized by abnormal secretion of protein into urine and ultimately end-stage renal failure. Clustering of the proteins, nephrin and Nck, have been suggested to be important for efficient signaling, though a mechanistic rationale for this is lacking. Studies from our lab have identified a novel regulation of N-WASP activity through dimerization, which increases N-WASP's activity in vitro by >100- fold. We hypothesize that Nck clustering regulates N-WASP dimerization in nephrin signaling, which we propose to study.